Dataset Information

Anogenital distance and penile length in infants with hypospadias or cryptorchidism: comparison with normative data.

ABSTRACT:

Background

Anogenital distance (AGD) in animals is a sensitive biomarker of fetal endocrine disruption and the associated testicular dysgenesis syndrome (TDS). However, AGD in human infants with cryptorchidism and hypospadias, which are potential manifestations of TDS during childhood, is not clearly described.

Objective

Our aim was to compare AGD in boys with cryptorchidism or hypospadias against normative data.

Methods

Boys with isolated cryptorchidism (n = 71, age 13.4 ± 5.8 months) or hypospadias (n = 81, age 11.4 ± 6.2 months) were recruited from a tertiary center for measurement of AGD and penile length; they were compared with 487 healthy full-term boys from a birth cohort by deriving age-specific standard deviation scores (SDS).

Results

Boys with cryptorchidism were older (p = 0.048) compared with boys with hypospadias. Boys with hypospadias had shorter mean AGD and penile length SDS than healthy boys (both p < 0.0001). Mean AGD and penile length SDS values in boys with cryptorchidism were longer than mean values in boys with hypospadias (both p < 0.01) and shorter than mean values in healthy boys (both p < 0.0001). Mean penile length SDS decreased as the severity of hypospadias increased (ptrend = 0.078).

Conclusions

In the study population, AGD and penile length were reduced in boys with hypospadias or cryptorchidism relative to normative data derived from a longitudinal birth cohort. The findings support the use of AGD as a quantitative biomarker to examine the prenatal effects of exposure to endocrine disruptors on the development of the male reproductive tract.

SUBMITTER: Thankamony A

PROVIDER: S-EPMC3915266 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Anogenital distance and penile length in infants with hypospadias or cryptorchidism: comparison with normative data.

Thankamony Ajay A Lek Ngee N Carroll Dan D Williams Martyn M Dunger David B DB Acerini Carlo L CL Ong Ken K KK Hughes Ieuan A IA

Environmental health perspectives 20131206 2

<h4>Background</h4>Anogenital distance (AGD) in animals is a sensitive biomarker of fetal endocrine disruption and the associated testicular dysgenesis syndrome (TDS). However, AGD in human infants with cryptorchidism and hypospadias, which are potential manifestations of TDS during childhood, is not clearly described.<h4>Objective</h4>Our aim was to compare AGD in boys with cryptorchidism or hypospadias against normative data.<h4>Methods</h4>Boys with isolated cryptorchidism (n = 71, age 13.4 ± ...[more]

PMID: 24316680

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Project description:Study questionWhat is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8-14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW?Summary answerIntrauterine paracetamol exposure during 8-14 weeks of gestation is associated with shorter AGD from birth to 24 months of age.What is already knownThe increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism.Study design, size, durationProspective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire.Participants/materials, setting, methodMothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (<8 weeks, 8-14 weeks and >14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8-14 weeks. AGD measurements were available for 434 male infants.Main results and the role of chanceParacetamol exposure during 8-14 weeks of gestation, but not any other period, was associated with shorter AGD (by 0.27 SD, 95% CI 0.06-0.48, P = 0.014) from birth to 24 months of age. This reduction was independent of body size. Paracetamol exposure was not related to penile length or testicular descent.Limitations, reasons for cautionConfounding by other drugs or endocrine-disrupting chemicals cannot be discounted. The cohort was not fully representative of pregnant women in the UK, particularly in terms of maternal ethnicity and smoking prevalence. There is likely to have been misclassification of paracetamol exposure due to recall error.Wider implications of the findingsOur observational findings support experimental evidence that intrauterine paracetamol exposure during the MPW may adversely affect male reproductive development.Study funding/competing interestsThis work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation for Disabled Children, the Evelyn Trust, the Mothercare Group Foundation, Mead Johnson Nutrition, and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. The authors declare no conflict of interest.

Project description:BackgroundAnogenital distance (AGD), the distance between the anus and genitals, is in rodents a well-established marker of early androgen action and has been suggested to be so in humans as well. Thus, a link between human AGD and semen quality and potentially fecundity may exist.ObjectiveThe aim of this study was to assess the association between AGD and male factor infertility and among proven fertile men also time to pregnancy (TTP).Material and methodsAll included men were recruited from and examined at Copenhagen University Hospital - Rigshospitalet, Denmark (N = 388). Men with impaired semen quality were included from infertile couples (N = 128), and men with naturally conceived pregnant partners were invited to participate when their partners had their routine second trimester examination (N = 260). All men underwent a physical examination, completed a questionnaire (including TTP for the fertile men), delivered a semen sample and had a blood sample drawn. The primary exposure was AGDAS measured from the centre of the anus to the posterior base of the scrotum. Associations between AGD and fertility status as well as between AGD and TTP among the fertile men were calculated using multiple logistic regression adjusted for covariates.ResultsAGD did not show a statistically significant association with fertility status. In adjusted logistic regression models, the odds of infertility per 1 cm increase in AGDAS were 1.02 (95% confidence interval [CI]: 0.88; 1.19). Among fertile men, a 1-cm increase in AGDAS was associated with an 8% non-statistically significantly reduced odds of having a longer (>3months) TTP (adjusted odds ratio (OR) = 0.92, 95% CI: 0.76-1.11).ConclusionOur study showed that the clinical application of AGD as a predictor of fertility and fecundity seems to be limited as no associations were observed between AGD and fertility status, nor was the decreased risk of experiencing a longer TTP with longer AGDAS statistically significant.

Project description:Study questionCould the anogenital distance (AGD) as assessed by MRI (MRI-AGD) be a diagnostic tool for endometriosis?Summary answerA short MRI-AGD is a strong diagnostic marker of endometriosis.What is known alreadyA short clinically assessed AGD (C-AGD) is associated with the presence of endometriosis.Study design size durationThis study is a re-analysis of previously published data from a case-control study.Participants/materials setting methodsWomen undergoing pelvic surgery from January 2018 to June 2019 and who had a preoperative pelvic MRI were included. C-AGD was measured at the beginning of the surgery by a different operator who was unaware of the endometriosis status. MRI-AGD was measured retrospectively by a senior radiologist who was blinded to the final diagnosis. Two measurements were made: from the posterior wall of the clitoris to the anterior edge of the anal canal (MRI-AGD-AC), and from the posterior wall of the vagina to the anterior edge of the anal canal (MRI-AGD-AF).Main results and the role of chanceThe study compared MRI-AGD of 67 women with endometriosis to 31 without endometriosis (controls). Average MRI-AGD-AF measurements were 13.3?mm (±3.9) and 21.2?mm (±5.4) in the endometriosis and non-endometriosis groups, respectively (P?<?10-5). Average MRI-AGD-AC measurements were 40.4?mm (±7.3) and 51.1?mm (±8.6) for the endometriosis and non-endometriosis groups, respectively (P?<?10-5). There was no difference of MRI-AGD in women with and without endometrioma (P?=?0.21), or digestive involvement (P?=?0.26). Moreover, MRI-AGD values were independent of the revised score of the American Society of Reproductive Medicine and the Enzian score. The diagnosis of endometriosis was negatively associated with both the MRI-AGD-AF (? = -7.79, 95% CI (-9.88; -5.71), P?<?0.001) and MRI-AGD-AC (? = -9.51?mm, 95% CI (-12.7; 6.24), P?<?0.001) in multivariable analysis. Age (? = +0.31?mm, 95% CI (0.09; 0.53), P?=?0.006) and BMI (? = +0.44?mm, 95% CI (0.17; 0.72), P?=?0.001) were positively associated with the MRI-AGD-AC measurements in multivariable analysis. MRI-AGD-AF had an AUC of 0.869 (95% CI (0.79; 0.95)) and outperformed C-AGD. Using an optimal cut-off of 20?mm for MRI-AGD-AF, a sensitivity of 97.01% and a specificity of 70.97% were noted.Limitations reasons for cautionThis was a retrospective analysis and no adolescents had been included.Wider implications of the findingsThis study is consistent with previous works associating a short C-AGD with endometriosis and the absence of correlation with the disease phenotype. MRI-AGD is more accurate than C-AGD in this setting and could be evaluated in the MRI examination of patients with suspected endometriosis.Study funding/competing interestsN/A.Trial registration numberThe protocol was approved by the 'Groupe Nantais d'Ethique dans le Domaine de la Santé' and registered under reference 02651077.

Dataset Information

Anogenital distance and penile length in infants with hypospadias or cryptorchidism: comparison with normative data.

Background

Objective

Methods

Results

Conclusions

Publications

Anogenital distance and penile length in infants with hypospadias or cryptorchidism: comparison with normative data.

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